IP Library › Patent Application 18597357
Patent Application
App. No. 18/597,357

CHIMERIC ANTIGEN RECEPTOR

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Patent No.
US None
App. No.
18/597,357
Abstract

The present invention provides a chimeric antigen receptor (CAR) which binds a target antigen having a bulky extra-cellular domain, wherein the CAR comprises a Fab antigen binding domain. The present invention also provides nucleic acid sequences and constructs encoding such a CAR, cells expressing such a CAR and their therapeutic uses.

Claims (89)

1 - 25 . (canceled)

26 . A method for killing a CD22-expressing target cell in a subject, the method comprising the step of administering to the subject a cell which expresses a chimeric antigen receptor (CAR) comprising an anti-CD22 antigen-binding domain which comprises:

a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences:

(SEQ ID No. 93)

CDR1 - NFAMA

(SEQ ID No. 94)

CDR2 - SISTGGGNTYYRDSVKG

(SEQ ID No. 95)

CDR3 - QRNYYDGSYDYEGYTMDA;

and

b) a light chain variable region (VL) having complementarity determining regions (CDRs) with the following sequences:

(SEQ ID NO: 96)

CDR1 - RSSQDIGNYLT,

(SEQ ID NO: 97)

CDR2 - GAIKLED, 

and

(SEQ ID NO: 98)

CDR3 - LQSIQYP.

27 . The method according to claim 26 , wherein the antigen-binding domain of the CAR comprises a VH domain having the sequence shown as SEQ ID NO: 65; and a VL domain having the sequence shown as SEQ ID NO: 66.

28 . The method according to claim 26 , wherein the cell further comprises a second CAR which is an anti-CD19 CAR.

29 . The method according to claim 28 , wherein the antigen binding domain of the anti-CD19 CAR comprises

a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences:

(SEQ ID NO: 69)

CDR1 - GYAFSSS,

(SEQ ID NO: 70)

CDR2 - YPGDED,

and

(SEQ ID NO: 71)

CDR3 - SLLYGDYLDY,

and

b) a light chain variable region (VL) having CDRs with the following sequences:

(SEQ ID NO: 72)

CDR1 - SASSSVSYMH,

(SEQ ID NO: 73)

CDR2 - DTSKLAS,

and

(SEQ ID NO: 74)

CDR3 - QQWNINPLT.

30 . The method according to claim 29 , wherein the antigen-binding domain of the anti-CD19 CAR comprises a VH domain as shown in SEQ ID NO: 75 and a VL domain as shown as SEQ ID NO: 76.

31 . A method for making a cell, which comprises the step of introducing into a cell a nucleic acid sequence encoding an anti-CD22 chimeric antigen receptor (CAR) which comprises an antigen-binding domain which comprises:

a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences:

(SEQ ID No. 93)

CDR1 - NFAMA

(SEQ ID No. 94)

CDR2 - SISTGGGNTYYRDSVKG

(SEQ ID No. 95)

CDR3 - QRNYYDGSYDYEGYTMDA;

and

b) a light chain variable region (VL) having complementarity determining regions (CDRs) with the following sequences:

(SEQ ID No. 96)

CDR1 - RSSQDIGNYLT

(SEQ ID No. 97)

CDR2 - GAIKLED

(SEQ ID No. 98)

CDR3 - LQSIQYP

32 . The method according to claim 31 , wherein the antigen-binding domain of the CAR comprises a VH domain having the sequence shown as SEQ ID NO: 65; and a VL domain having the sequence shown as SEQ ID NO: 66.

33 . The method according to claim 31 , wherein the nucleic acid sequence comprises a first nucleic acid sequence encoding an anti-CD22 CAR and a second nucleic acid sequence encoding an anti-CD19 CAR.

34 . The method according to claim 33 , wherein the antigen binding domain of the anti-CD19 CAR comprises:

a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences:

(SEQ ID NO: 69)

CDR1 - GYAFSSS,

(SEQ ID NO: 70)

CDR2 - YPGDED,

and

(SEQ ID NO: 71)

CDR3 - SLLYGDYLDY,

and

b) a light chain variable region (VL) having CDRs with the following sequences:

(SEQ ID NO: 72)

CDR1 - SASSSVSYMH,

(SEQ ID NO: 73)

CDR2 - DTSKLAS,

and

(SEQ ID NO: 74)

CDR3 - QQWNINPLT.

35 . The method according to claim 34 , wherein the antigen-binding domain of the anti-CD19 CAR comprises a VH domain as shown in SEQ ID NO: 75 and a VL domain as shown as SEQ ID NO: 76.

36 . The method according to claim 33 , wherein the anti-CD22 CAR is in an scFv format, the nucleic acid sequence having the general structure:

AgBD1-spacer1-TM1-endo1-coexpr-AgBD2-spacer2-TM2-endo2 or

AgBD2-spacer2-TM2-endo2-coexpr-AgBD1-spacer1-TM1-endo1,

wherein:

AgBD1 is a nucleic acid sequence encoding an antigen binding domain of the first CAR,

Spacer1 is a nucleic acid sequence encoding a spacer of the first CAR,

TM1 is a nucleic acid sequence encoding a transmembrane domain of the first CAR,

Endo1 is a nucleic acid sequence encoding an endodomain of the first CAR,

Coexpr is a nucleic acid sequence enabling co-expression of the first and second CARS,

AgBD2 is a nucleic acid sequence encoding an antigen binding domain of the second CAR,

Spacer2 is a nucleic acid sequence encoding a spacer of the second CAR,

TM2 is a nucleic acid sequence encoding a transmembrane domain of the second CAR, and

Endo2 is a nucleic acid sequence encoding an endodomain of the second CAR.

Assignments (2)
PATENT SECURITY AGREEMENT Recorded Jul 30, 2026
From: AUTOLUS LIMITED
To: PERCEPTIVE CREDIT HOLDINGS V, LP, AS ADMINISTRATIVE AGENT
Reel/Frame 076084/0283 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 19, 2024
From: PULÉ, MARTIN; KOKALAKI, EVANGELIA; CORDOBA, SHAUN; ONUOHA, SHIMOBI; THOMAS, SIMON; MA, BIAO; FERRARI, MATHIEU
To: AUTOLUS LIMITED
Reel/Frame 068632/0146 →